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Article ; Online: APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer.

2023 Volume 55, Issue 10, Page(s) 1721–1734

Abstract: ... interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R ... loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B ... landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions ...

Abstract	The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer.
MeSH term(s)	Humans ; R-Loop Structures ; DNA, Single-Stranded/genetics ; Genome-Wide Association Study ; Mutagenesis ; Neoplasms/genetics ; Neoplasms/pathology ; Cytidine Deaminase/genetics ; Minor Histocompatibility Antigens/genetics ; Minor Histocompatibility Antigens/metabolism
Chemical Substances	DNA, Single-Stranded ; Cytidine Deaminase (EC 3.5.4.5) ; Minor Histocompatibility Antigens ; APOBEC3B protein, human (EC 3.5.4.5)
Language	English
Publishing date	2023-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01504-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Book ; Online: R-MelNet

Kastner, Kyle / Courville, Aaron

Reduced Mel-Spectral Modeling for Neural TTS

2022

Abstract: This paper introduces R-MelNet, a two-part autoregressive architecture with a frontend based ... to produce an audio waveform. Coupled with half precision training, R-MelNet uses under 11 gigabytes of GPU ... quantitative evaluations of an R-MelNet system trained on a single speaker TTS dataset demonstrate the effectiveness ...

Abstract	This paper introduces R-MelNet, a two-part autoregressive architecture with a frontend based on the first tier of MelNet and a backend WaveRNN-style audio decoder for neural text-to-speech synthesis. Taking as input a mixed sequence of characters and phonemes, with an optional audio priming sequence, this model produces low-resolution mel-spectral features which are interpolated and used by a WaveRNN decoder to produce an audio waveform. Coupled with half precision training, R-MelNet uses under 11 gigabytes of GPU memory on a single commodity GPU (NVIDIA 2080Ti). We detail a number of critical implementation details for stable half precision training, including an approximate, numerically stable mixture of logistics attention. Using a stochastic, multi-sample per step inference scheme, the resulting model generates highly varied audio, while enabling text and audio based controls to modify output waveforms. Qualitative and quantitative evaluations of an R-MelNet system trained on a single speaker TTS dataset demonstrate the effectiveness of our approach.
Keywords	Computer Science - Sound ; Computer Science - Machine Learning ; Electrical Engineering and Systems Science - Audio and Speech Processing
Subject code	006
Publishing date	2022-06-30
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Rates of Positive M-CHAT-R Screenings by Pandemic Birth and Prenatal SARS-CoV-2 Exposure

Firestein, Morgan R. / Manessis, Angela Gigliotti / Warmingham, Jen / Hu, Yunzhe / Finkel, Morgan A. / Kyle, Margaret / Hussain, Maha / Ahmed, Imaal / Lavallée, Andréane / Solis, Ana / Chaves, Vitoria / Rodriguez, Cynthia / Goldman, Sylvie / Muhle, Rebecca A. / Lee, Seonjoo / Austin, Judy / Silver, Wendy G. / O’Reilly, Kally C. / Bain, Jennifer M. /

Penn, Anna A. / Veenstra-VanderWeele, Jeremy / Stockwell, Melissa S. / Fifer, William P. / Marsh, Rachel / Monk, Catherine / Shuffrey, Lauren C. / Dumitriu, Dani

medRxiv

Abstract: ... in Toddlers-Revised (M-CHAT-R). Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative ... Participants completed the M-CHAT-R as part of routine clinical care (COMBO-EHR cohort) or for research ... hospitals between 2018-2023 and who had a valid M-CHAT-R score in their health record. The COMBO-RSCH cohort ...

Abstract	Maternal stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Children born during the COVID-19 pandemic, including those exposed prenatally to maternal SARS-CoV-2 infections, are reaching the developmental age for the assessment of risk for neurodevelopmental conditions. We examined associations between birth during the COVID-19 pandemic, prenatal exposure to maternal SARS-CoV-2 infection, and rates of positive screenings on the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. Participants completed the M-CHAT-R as part of routine clinical care (COMBO-EHR cohort) or for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 status during pregnancy was determined through electronic health records. The COMBO-EHR cohort includes n=1664 children (n=442 historical cohort, n=1222 pandemic cohort; n=997 SARS-CoV-2 unexposed prenatally, n=130 SARS-CoV-2 exposed prenatally) who were born at affiliated hospitals between 2018-2023 and who had a valid M-CHAT-R score in their health record. The COMBO-RSCH cohort consists of n=359 children (n=268 SARS-CoV-2 unexposed prenatally, n=91 SARS-CoV-2 exposed prenatally) born at the same hospitals who enrolled into a prospective cohort study that included administration of the M-CHAT-R at 18-months. Birth during the pandemic was not associated with greater likelihood of a positive M-CHAT-R screen in the COMBO-EHR cohort. Maternal SARS-CoV-2 was associated with lower likelihood of a positive M-CHAT-R screening in adjusted models in the COMBO-EHR cohort (OR=0.40, 95% CI=0.22 - 0.68, p=0.001), while analyses in the COMBO-RSCH cohort yielded similar but non-significant results (OR=0.67, 95% CI=0.31-1.37, p=0.29). These results suggest that children born during the first 18 months of the COVID-19 pandemic and those exposed prenatally to a maternal SARS-CoV-2 infection are not at greater risk for screening positive on the M-CHAT-R.
Keywords	covid19
Language	English
Publishing date	2024-02-22
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2024.02.20.24302892
Database	COVID19

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Article ; Online: The evidence synthesis and meta-analysis in R conference (ESMARConf): levelling the playing field of conference accessibility and equitability.

Haddaway, Neal R / Bannach-Brown, Alexandra / Grainger, Matthew J / Hamilton, W Kyle / Hennessy, Emily A / Keenan, Ciara / Pritchard, Chris C / Stojanova, Jana

Systematic reviews

2022 Volume 11, Issue 1, Page(s) 113

Abstract: ... in collaborative digital and programmatic frameworks, such as the free and Open Source software R, have ... Despite this, evidence synthesis (and meta-analysis) practitioners and methodologists who make use of R ... synthesis and meta-analysis in the R programming environment (ESMARConf) that aims to connect ...

Abstract	Rigorous evidence is vital in all disciplines to ensure efficient, appropriate, and fit-for-purpose decision-making with minimised risk of unintended harm. To date, however, disciplines have been slow to share evidence synthesis frameworks, best practices, and tools amongst one another. Recent progress in collaborative digital and programmatic frameworks, such as the free and Open Source software R, have significantly expanded the opportunities for development of free-to-use, incrementally improvable, community driven tools to support evidence synthesis (e.g. EviAtlas, robvis, PRISMA2020 flow diagrams and metadat). Despite this, evidence synthesis (and meta-analysis) practitioners and methodologists who make use of R remain relatively disconnected from one another. Here, we report on a new virtual conference for evidence synthesis and meta-analysis in the R programming environment (ESMARConf) that aims to connect these communities. By designing an entirely free and online conference from scratch, we have been able to focus efforts on maximising accessibility and equity-making these core missions for our new community of practice. As a community of practice, ESMARConf builds on the success and groundwork of the broader R community and systematic review coordinating bodies (e.g. Cochrane), but fills an important niche. ESMARConf aims to maximise accessibility and equity of participants across regions, contexts, and social backgrounds, forging a level playing field in a digital, connected, and online future of evidence synthesis. We believe that everyone should have the same access to participation and involvement, and we believe ESMARConf provides a vital opportunity to push for equitability across disciplines, regions, and personal situations.
MeSH term(s)	Humans ; Software
Language	English
Publishing date	2022-06-03
Publishing country	England
Document type	Letter ; Meta-Analysis
ZDB-ID	2662257-9
ISSN	2046-4053 ; 2046-4053
ISSN (online)	2046-4053
ISSN	2046-4053
DOI	10.1186/s13643-022-01985-6
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Article ; Online: Clinical and Mechanistic Implications of R-Loops in Human Leukemias.

Lee, Seo-Yun / Miller, Kyle M / Kim, Jae-Jin

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: ... with genomic instability. R-loops are three-stranded nucleic acid structures consisting of an RNA-DNA hybrid and a non ... replication, and DSB repair. However, unregulated R-loop formation can cause DNA damage and ... understanding of aberrant R-loop formation and how it influences genomic instability and leukemia development ...

Abstract	Genetic mutations or environmental agents are major contributors to leukemia and are associated with genomic instability. R-loops are three-stranded nucleic acid structures consisting of an RNA-DNA hybrid and a non-template single-stranded DNA. These structures regulate various cellular processes, including transcription, replication, and DSB repair. However, unregulated R-loop formation can cause DNA damage and genomic instability, which are potential drivers of cancer including leukemia. In this review, we discuss the current understanding of aberrant R-loop formation and how it influences genomic instability and leukemia development. We also consider the possibility of R-loops as therapeutic targets for cancer treatment.
MeSH term(s)	Humans ; R-Loop Structures ; Transcription, Genetic ; DNA Repair ; RNA/genetics ; DNA Replication ; Leukemia/genetics ; Genomic Instability
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065966
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Article ; Online: The evidence synthesis and meta-analysis in R conference (ESMARConf)

Neal R. Haddaway / Alexandra Bannach-Brown / Matthew J. Grainger / W. Kyle Hamilton / Emily A. Hennessy / Ciara Keenan / Chris C. Pritchard / Jana Stojanova

Systematic Reviews, Vol 11, Iss 1, Pp 1-

levelling the playing field of conference accessibility and equitability

2022 Volume 9

Abstract: ... progress in collaborative digital and programmatic frameworks, such as the free and Open Source software R ... use of R remain relatively disconnected from one another. Here, we report on a new virtual conference ... for evidence synthesis and meta-analysis in the R programming environment (ESMARConf) that aims to connect ...

Abstract	Abstract Rigorous evidence is vital in all disciplines to ensure efficient, appropriate, and fit-for-purpose decision-making with minimised risk of unintended harm. To date, however, disciplines have been slow to share evidence synthesis frameworks, best practices, and tools amongst one another. Recent progress in collaborative digital and programmatic frameworks, such as the free and Open Source software R, have significantly expanded the opportunities for development of free-to-use, incrementally improvable, community driven tools to support evidence synthesis (e.g. EviAtlas, robvis, PRISMA2020 flow diagrams and metadat). Despite this, evidence synthesis (and meta-analysis) practitioners and methodologists who make use of R remain relatively disconnected from one another. Here, we report on a new virtual conference for evidence synthesis and meta-analysis in the R programming environment (ESMARConf) that aims to connect these communities. By designing an entirely free and online conference from scratch, we have been able to focus efforts on maximising accessibility and equity—making these core missions for our new community of practice. As a community of practice, ESMARConf builds on the success and groundwork of the broader R community and systematic review coordinating bodies (e.g. Cochrane), but fills an important niche. ESMARConf aims to maximise accessibility and equity of participants across regions, contexts, and social backgrounds, forging a level playing field in a digital, connected, and online future of evidence synthesis. We believe that everyone should have the same access to participation and involvement, and we believe ESMARConf provides a vital opportunity to push for equitability across disciplines, regions, and personal situations.
Keywords	Online conference ; Equity ; Pay-it-forwards ; Volunteer ; Systematic review ; Synthesis ; Medicine ; R
Subject code	028
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: gPKPDviz: A flexible R shiny tool for pharmacokinetic/pharmacodynamic simulations using mrgsolve.

Lu, Tong / Poon, Victor / Brooks, Logan / Velasquez, Erick / Anderson, Eric / Baron, Kyle / Jin, Jin Y / Kågedal, Matts

CPT: pharmacometrics & systems pharmacology

2023 Volume 13, Issue 3, Page(s) 341–358

Abstract: ... for the mrgsolve model, providing the same error messages as model compilation in R. GPKPDviz has had stringent ... validation by comparing simulation results between the app and using mrgsolve in R. GPKPDviz is a member ...

Abstract	GPKPDviz is a Shiny application (app) dedicated to real-time simulation, visualization, and assessment of the pharmacokinetic/pharmacodynamic (PK/PD) models. Within the app, gPKPDviz is capable of generating virtual populations and complex dosing and sampling scenarios, which, together with the streamlined workflow, is designed to efficiently assess the impact of covariates and dosing regimens on PK/PD end points. The actual population data from clinical trials can be loaded into the app for simulation if desired. The app-generated dosing regimens include single or multiple dosing, and more complex regimens, such as loading doses or intermittent dosing. When necessary, the dosing regimens can be defined externally and loaded to the app for simulation. Using mrgsolve as the simulation engine, gPKPDviz is typically used for population simulation, however, with a slight modification of the mrgsolve model, gPKPDviz is capable of performing individual simulations with individual post hoc parameters, individual dosing logs, and individual sampling timepoints through an external dataset. A built-in text editor has a debugging feature for the mrgsolve model, providing the same error messages as model compilation in R. GPKPDviz has had stringent validation by comparing simulation results between the app and using mrgsolve in R. GPKPDviz is a member of the suite of Modeling and Simulation Shiny apps developed at Genentech to facilitate the typical modeling work in Clinical Pharmacology. For broader access to the Pharmacometric community, gPKPDviz has been published as an open-source application in GitHub under the terms of GNU General Public License.
MeSH term(s)	Computer Simulation ; Models, Biological
Language	English
Publishing date	2023-12-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2697010-7
ISSN	2163-8306 ; 2163-8306
ISSN (online)	2163-8306
ISSN	2163-8306
DOI	10.1002/psp4.13096
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Article ; Online: {NCIFD} — An Internal R Package for a Fisheries Agency

Wheeler, A. Powell / Rachels, Kyle T. / Dockendorf, Kevin J.

Fisheries. 2023 Oct., v. 48, no. 10 p.411-417

2023

Abstract: We developed an R package for the Inland Fisheries Division of the North Carolina Wildlife ... Resources Commission to help team members share R functions and data sets. The {NCIFD} package stores ... from a database of standardized fish samples and imports the data into an R session. In addition, {NCIFD} stores ...

Abstract	We developed an R package for the Inland Fisheries Division of the North Carolina Wildlife Resources Commission to help team members share R functions and data sets. The {NCIFD} package stores several functions that were developed for agency research, including cleanBIODE(), which cleans query results from a database of standardized fish samples and imports the data into an R session. In addition, {NCIFD} stores a variety of data sets including observations from ongoing research projects, hatchery records, and administrative information. Stored in a package, data sets are instantly available for exploration and analysis in an R session, can share a common naming convention, and retain their metadata. Although developing an R package requires effort, we believe it is a useful tool that other fisheries agencies should encourage interested staff to explore. We share advice to help others get started while avoiding some missteps we encountered.
Keywords	databases ; fish ; hatcheries ; metadata ; wildlife ; North Carolina
Language	English
Dates of publication	2023-10
Size	p. 411-417.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	430448-2
ISSN	0363-2415
ISSN	0363-2415
DOI	10.1002/fsh.10974
Database	NAL-Catalogue (AGRICOLA)

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Book ; Online: Super-R BiFeO$_3$

Paull, Oliver / Xu, Changsong / Cheng, Xuan / Zhang, Yangyang / Xu, Bin / Kelley, Kyle / Collins, Liam / de Marco, Alex / Vasudevan, Rama K. / Bellaiche, Laurent / Nagarajan, Valanoor / Sando, Daniel

Epitaxial stabilization of a low-symmetry phase with giant electromechanical response

2021

Abstract: Piezoelectrics interconvert mechanical energy and electric charge and are widely used in actuators and sensors. The best performing materials are ferroelectrics at a morphotropic phase boundary (MPB), where several phases can intimately coexist. ... ...

Abstract	Piezoelectrics interconvert mechanical energy and electric charge and are widely used in actuators and sensors. The best performing materials are ferroelectrics at a morphotropic phase boundary (MPB), where several phases can intimately coexist. Switching between these phases by electric field produces a large electromechanical response. In the ferroelectric BiFeO$_3$, strain can be used to create an MPB-like phase mixture and thus to generate large electric field dependent strains. However, this enhanced response occurs at localized, randomly positioned regions of the film, which potentially complicates nanodevice design. Here, we use epitaxial strain and orientation engineering in tandem - anisotropic epitaxy - to craft a hitherto unavailable low-symmetry phase of BiFeO$_3$ which acts as a structural bridge between the rhombohedral-like and tetragonal-like polymorphs. Interferometric displacement sensor measurements and first-principle calculations reveal that under external electric bias, this phase undergoes a transition to the tetragonal-like polymorph, generating a piezoelectric response enhanced by over 200%, and associated giant field-induced reversible strain. These results offer a new route to engineer giant electromechanical properties in thin films, with broader perspectives for other functional oxide systems. Comment: 20 pages, 4 figures
Keywords	Condensed Matter - Materials Science
Publishing date	2021-01-31
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protocol for identification and computational analysis of human natural killer cells using flow cytometry and R.

Kroll, Kyle / Reeves, R Keith

STAR protocols

2023 Volume 4, Issue 1, Page(s) 102044

Abstract: ... human NK cells using flow gating, data export from FlowJo, data loading in R, dimensionality reduction ...

Abstract	Identifying differential protein expression is routinely used to delineate natural killer (NK) cells from various sample cohorts. This protocol describes key steps for NK cell analysis: identifying human NK cells using flow gating, data export from FlowJo, data loading in R, dimensionality reduction and visualization with Uniform Manifold Approximation and Projection, and generalized linear modeling with CyotGLMM. These analyses can help generate potential biomarkers of interest to identify NK cells across aging, treatment groups, and others. For complete details on the use and execution of this protocol, please refer to Kroll et al. (2022).
MeSH term(s)	Humans ; Flow Cytometry/methods ; Killer Cells, Natural ; Biomarkers/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102044
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